In order to determine the incidence of renal lithiasis in patients with renal tubular acidosis and the effect of therapy on further stone formation, we reviewed the clinical and laboratory manifestations, X-ray findings, and treatment of 48 patients with renal tubular acidosis who were seen at the Mayo Clinic during the years 1970-1980. Thirty-four patients (70%) had radiological evidence of renal lithiasis which was the presenting symptom in 23 (48%) patients. In every instance the calculi were multiple and, with one exception, bilateral. While receiving therapy, 19 patients with renal lithiasis were followed for longer than one year with sequential uroradiographic studies. Fifteen of these patients were treated with oral base alone and thirteen had no evidence of new stone formation or continued growth of existing stones during therapy. The two patients with X-ray evidence of continued stone formation admitted to poor compliance. Four patients received initial treatment with an oral phosphorus supplement. Three of these four patients had radiographic evidence of continued renal stone formation during three, five and eight years of phosphate therapy. We conclude renal lithiasis is a frequent complication of renal tubular acidosis, and adequate base replacement is effective therapy to stop continued stone formation while oral phosphate therapy alone is often ineffective.